Lavoie Brigitte, Lian Jane B, Mawe Gary M
Department of Neurological Sciences, The University of Vermont, Burlington, VT, 05405, USA.
The University of Vermont, D406 Given Building, Burlington, VT, 05405, USA.
Adv Exp Med Biol. 2017;1033:35-46. doi: 10.1007/978-3-319-66653-2_3.
The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.
骨骼生长和更新过程受到多种信号分子作用的严格调控，这些信号分子包括激素、生长因子和细胞因子。这些过程的失衡会导致骨骼疾病，如骨质疏松症或高骨量疾病。越来越清楚的是，血清素可以通过多种机制并在身体的不同部位发挥作用，以影响骨形成和骨吸收之间的平衡。其对骨代谢的作用可能会有所不同，这取决于其合成部位（中枢或外周）以及被激活的受体的细胞和亚型。在中枢神经系统中，血清素能神经元通过下丘脑发挥作用，抑制对骨骼的交感神经输入。由于交感神经输入会抑制骨形成，因此脑血清素对骨骼生长具有净正向作用。肠道来源的血清素被认为通过激活前成骨细胞上的受体来减弱成骨细胞增殖，从而抑制骨骼生长。也有证据表明血清素可以在骨骼内合成并作用于调节骨代谢。成骨细胞、破骨细胞和骨细胞都具备合成血清素的机制，并且它们还表达血清素再摄取转运体（SERT）。了解血清素在骨骼塑形和重塑的紧密平衡系统中的作用是一个具有临床相关性的目标。这一知识可以阐明影响血清素信号传导的药物的骨骼相关副作用，包括血清素特异性再摄取抑制剂（SSRI）以及受体激动剂和拮抗剂，并且可能会带来缓解骨骼病变的治疗方法。
